Search Results (641)

Alcohol Use Disorder (AUD) poses global health challenges, and causes hematological alterations such as macrocytosis and oxidative stress. Disruption of protein structures by alcohol and/or its metabolites may exacerbate AUDs; proteomics can elucidate the underlying biological mechanisms. This study examined the proteins differentially expressed in the cytosol and membrane fractions of erythrocytes obtained from 30 male patients with AUD, comparing them to samples from 15 age- and BMI-matched social drinkers (SDs) and 15 non-drinkers (control). The analysis aimed to identify the molecular differences related to alcohol consumption. The AUD patient subgrouping was based on mean corpuscular volume (MCV), with 16 individuals classified as having a normal MCV and 14 having a high MCV. Proteins were separated via two-dimensional(2D)-gel electrophoresis, digested with trypsin, and identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (TOF) mass spectrometry (MALDI-TOF/TOF). Additionally, levels of malondialdehyde and 4-hydroxyalkenals (MDA + HAE), reduced glutathione (GSH), oxidized glutathione (GSSG), serum carbohydrate-deficient transferrin (%CDT), disialotransferrin (%DST), and sialic acid (SA) were analyzed. The results showed increased MDA + HAE and decreased total thiols in AUD patients, with GSSG elevated and the GSH/GSSG ratio reduced in the AUD MCV-high subgroup. Serum %CDT, %DST, and SA were significantly higher in AUD. Compared to the control profiles, the AUD group exhibited differential protein expression. Few proteins, such as bisphosphoglycerate mutase, were downregulated in AUD versus control and SD, as well as in the MCV-high AUD subgroup. Conversely, endoplasmin and gelsolin were upregulated in AUD relative to control. Cytoskeletal proteins, including spectrin-alpha chain, actin cytoplasmic 2, were overexpressed in the AUD group and MCV-high AUD subgroup. Several proteins, such as 14-3-3 isoforms, alpha-synuclein, translation initiation factors, heat shock proteins, and others, were upregulated in the MCV-high AUD subgroup. Under-expressed proteins in this subgroup include band 3 anion transport protein, bisphosphoglycerate mutase, tropomyosin alpha-3 chain, uroporphyrinogen decarboxylase, and WD repeat-containing protein 1. Our findings highlight the specific changes in protein expression associated with oxidative stress, cytoskeletal alterations, and metabolic dysregulation, specifically in AUD patients with an elevated MCV. Understanding these mechanisms is crucial for developing targeted interventions and identifying biomarkers of alcohol-induced cellular damage. The complex interplay between oxidative stress, membrane composition, and cellular function illustrates how chronic alcohol exposure affects cellular physiology. Full article

Objectives: Sex-based disparities in COVID-19 outcomes are well-documented, with men experiencing greater acute severity and women showing increased vulnerability to post-viral syndromes. However, longitudinal immunometabolic trajectories in vaccinated individuals remain underexplored. In this study, sex-based differences in long-term metabolic, endocrine, renal, cardiovascular, and inflammatory responses were investigated among vaccinated individuals recovering from SARS-CoV-2 infection. Methods: This retrospective single-center cohort study included 426 adults (199 females, 227 males) with PCR-confirmed symptomatic COVID-19 and at least two vaccine doses. Serial assessments were conducted at baseline, 18-, 24-, and 30-month post-infection. Parameters included fasting glucose, HbA1c, lipid profile, thyroid function, renal markers, CRP, D-dimer, fibrinogen, troponin, and hematologic indices. Statistical analyses assessed longitudinal changes and sex-stratified correlations. Results: Fasting glucose and HbA1c levels significantly declined over time, more prominently in males. Glucose correlated with age and BMI only in females. Lipid levels remained largely unchanged, although males had higher baseline triglycerides. Females showed rising TSH levels and persistently lower free T3; males exhibited higher creatinine, urea, and troponin levels throughout. Inflammatory markers declined significantly in both sexes, with males displaying higher CRP and troponin, and females showing sustained fibrinogen elevation and a temporary lymphocyte surge. D-dimer was elevated in females at the 30-month point. Conclusions: Sex-specific physiological recovery patterns were evident among vaccinated COVID-19 survivors. Males exhibited earlier metabolic and cardiac alterations, while females had more persistent endocrine and inflammatory shifts. These findings underscore the need for sex-tailored long-term monitoring strategies prioritizing early metabolic and cardiac screening in men and prolonged immunoendocrine surveillance in women. Full article

The deformability of red blood cells (RBCs) is critical for microvascular circulation and is impaired in hematological disorders such as thalassemia, a prevalent public health concern in Guangdong, China. While microfluidics enable high-precision deformability assessment, current studies lack standardization in deformation metrics and rarely investigate post-deformation recovery dynamics. This study introduces an automated microfluidic platform for systematically evaluating RBC deformability in healthy and thalassemic individuals. A biomimetic chip featuring 4 µm, 8 µm, and 16 µm wide channels (7 µm in height) was designed to simulate capillary dimensions, with COMSOL CFD numerical modeling validating shear stress profiles. RBC suspensions (10⁷ cells/mL in DPBS) were hydrodynamically focused through constrictions while high-speed imaging (15,000 fps) captured deformation–recovery dynamics. Custom-built algorithms with deep-learning networks automated cell tracking, contour analysis, and multi-parametric quantification. Validation confirmed significantly reduced deformability in Paraformaldehyde (PFA)-treated RBCs compared to normal controls. Narrower channels and higher flow velocities amplified shear-induced deformations, with more deformable cells exhibiting faster post-constriction shape recovery. Crucially, the platform distinguished thalassemia patient-derived RBCs from healthy samples, revealing significantly lower deformability in diseased cells, particularly in 4 µm channels. These results establish a standardized, high-throughput framework for RBC mechanical characterization, uncovering previously unreported recovery dynamics and clinically relevant differences in deformability in thalassemia. The method’s diagnostic sensitivity highlights its translational potential for screening hematological disorders. Full article

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article

The rise in antimicrobial resistance and strict milk withdrawal regulations drive the search for safe, non-antibiotic intramammary therapies. This pilot field study focused on clinical parameters, including the somatic cell count (SCC) and the assessment of changes, as well as overall safety, which together enabled a prospective evaluation of whether the substance exerted any therapeutic effect. In this study, 48 Holstein–Friesian cows with naturally occurring clinical mastitis (somatic cell count > 400,000 cells/mL; single quarter) were randomized to receive either seven daily infusions of 10% pectin (n = 24) or two standard intramammary doses of a licensed multi-component antibiotic formulation (n = 24). The clinical severity scores (0–3) and SCC were monitored from 72 h before to 168 h after treatment initiation; the bacteriological cultures, milk TNF-α, milk yield, and blood hematology/biochemistry were also assessed. Both groups exhibited comparable and significant reductions in the mastitis scores and log₂-transformed SCC by 48 h post-treatment, with equivalent bacteriological cure rates and pathogen profiles (predominantly Streptococcus uberis, coagulase-negative staphylococci, and Escherichia coli) and no local irritation, systemic adverse effects, or alterations in the milk yield, TNF-α, or blood parameters. These findings indicate that intramammary pectin at a 10% concentration is safe and well tolerated and that it provides efficacy equivalent to standard antibiotic therapy, supporting its potential as an alternative mastitis treatment that avoids antibiotic residues and contributes to antimicrobial stewardship. Full article

Background: We examined changes in hematological, biochemical, and hormonal biomarkers, along with endurance and explosive performance indices, in amateur soccer players over a 4-week preseason period. Methods: Thirteen players (age: 19.7 ± 2.0 years; body mass: 73.0 ± 6.8 kg; height: 180 ± 0.1 cm; body fat: 8.6 ± 3.5%) were monitored during a 4-week preseason program, which included 21 training days, three friendly matches, and four days of rest. Before and after this period, endurance capacity was evaluated using the Yo-Yo IR1 test, and leg power was assessed using the CMJ. Blood samples were collected for three consecutive days in week 1 and after week 4 to assess hematological and biochemical parameters. Internal load during all weeks was assessed with session RPE (sRPE). Results: There was a 25.5% increase in Yo-Yo IR1 distance (2123 ± 413 vs. 1560 ± 356 m, p = 0.002), with the estimated VO₂max and the speed associated with VO₂max (vVO₂max) improving by 8.7% (49.5 ± 3.0 to 54.2 ± 3.5 mL/kg/min, p = 0.002) and 5.3% (16.0 ± 0.7 to 16.9 ± 0.6 km/h, p = 0.002), respectively. In contrast, CMJ performance in weeks 2–4 declined by 13.4–21.0% relative to baseline, while sRPE peaked during week 3 (4011 ± 440 AU). Hematological variables were mostly stable except for small increases in MCV and MCH (1.5–1.8%, p < 0.001), while there were significant reductions in urea (12%), uric acid (6.2%), and erythropoietin (33%). Conclusions: A 4-week preseason program substantially improved aerobic capacity yet compromised leg power. Changes in biomarker profiles suggest that the training load maintained an appropriate balance between overload and recovery. These findings provide valuable guidance for coaches seeking to optimize training protocols while minimizing the risk of overtraining and preventing injuries during the competitive season. Full article

Lasia spinosa Thwaites (LST) has emerged as a potential supplement for enhancing male reproductive performance. This study evaluated the effects of long-term oral supplementation with LST on hematological parameters, semen characteristics, ultrasonographic measurements of the prostate gland and testes, and the cryopreservation potential of canine sperm. Six healthy male dogs received oral LST supplementation at a dosage of 10 mg/kg body weight once daily for 7 days (short-term). After a three-month washout period to ensure full physiological recovery, the same dogs underwent a long-term supplementation protocol (60 days). In the short-term trial, no clinically significant changes were observed in hematological or serum biochemical parameters, including complete blood count, alanine aminotransferase, creatinine, blood urea nitrogen, total protein, and albumin; all parameters were within normal reference ranges. Serum testosterone levels and semen characteristics were also unaffected (p > 0.05). During the long-term treatment, blood profiles and testosterone levels remained stable. Although prostatic and testicular volumes increased slightly, the changes were not statistically significant (p > 0.05). A significant increase in semen volume was observed (p < 0.05), while other semen parameters showed no significant differences. Notably, post-thaw sperm motility significantly improved at both 15 min and 4 h after thawing, and sperm viability was significantly enhanced at 4 h post-thaw (p < 0.05), suggesting a potential protective effect of LST during cryopreservation. These findings indicate that LST supplementation is physiologically safe and may improve canine sperm quality during freezing and thawing, supporting its potential application in reproductive health management. Full article

Background/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine–dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods/Results: UV–vis and ¹H-NMR spectroscopy confirmed the formation of a stable iodine–dextrin complex, with triiodide anions stabilized by hydrogen bonding and donor–acceptor interactions. No clinical signs of acute toxicity were observed at doses up to 5000 mg/kg, and subacute administration (62.5 and 125 mg/kg) showed no adverse effects on hematological or biochemical parameters. A mild, non-pathological enlargement of thyrocytes and parallel increases in TSH, T3, and T4 levels were observed at 125 mg/kg, consistent with physiological adaptation to iodine. Pharmacokinetic analysis revealed high oral bioavailability (~92%), prolonged half-life (~21 h), and wide tissue distribution with low clearance. In the sepsis model, pretreatment with AZ+PA alleviated clinical symptoms, maintained body weight, and significantly improved hematological parameters, reducing WBCs and CRP levels. The combination also decreased plasma IL-6 and TNF-α concentrations more effectively than either agent alone, indicating a synergistic anti-inflammatory effect. Histological analysis confirmed that PA, particularly in combination with AZ, mitigated LPS-induced tissue injury in the liver, kidney, and lungs. Conclusions: These findings suggest that PA is a safe, bioavailable compound with immunomodulatory properties that enhance azithromycin’s protective effects during systemic inflammation. This supports its potential use as a prophylactic agent in clinical settings, such as preoperative immune modulation to prevent sepsis-related complications. Full article

Cardiovascular disease (CVD) remains the leading global cause of morbidity and mortality, largely driven by atherosclerosis, a chronic inflammatory process involving lipids and immune cells. Although traditional lipid biomarkers such as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) are well-established in CVD risk stratification, the interplay between cytokines, chemokines, growth factors (CCGFs), lipid metabolism, and hematological parameters in non-cardiac populations remains underexplored. We investigated associations between plasma cytokines and lipid-related biomarkers and their relationships with circulating blood cell counts in a cohort of 164 essentially healthy adults aged 18–44 years. CCGF profiling was performed using a proximity extension assay (PEA), and statistical correlations were adjusted for multiple testing using false discovery rate (FDR) correction. The CCGFs that were associated with HDL and apolipoprotein A1 all displayed negative associations. Several pro-inflammatory cytokines, including CCL3, IL-6, and TNFSF10, showed strong positive associations with triglycerides, remnants, non-HDL, and body mass index (BMI). Furthermore, triglycerides and remnants were consistently correlated with elevated leukocyte, neutrophil, and platelet counts. HGF and FGF-21, mainly considered as anti-inflammatory, were positively associated with BMI and negatively associated with HDL, which is compliant with a multitude of actions, depending on the local milieu and the cellular interplay. Our results support the existence of a complex immunometabolic network involving lipids, CCGFs, and blood cells, even in non-diseased individuals. The observed patterns underscore the importance of understanding the intricate cytokine–lipid–cell interactions that may occur in early pathophysiological processes and highlight their potential utility in refining cardiovascular risk assessment beyond traditional lipid metrics. Full article

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

Growing freshwater fish in saline environments is being explored as a potential solution to the freshwater shortage. However, growing these organisms in suboptimal salinity conditions leads to chronic stress that can be challenging to manage. To address this goal, it is crucial to improve the health of fish through the use of dietary supplements. This study evaluated the effects of varying levels of arginine supplementation on the growth, health status, and expression of stress-related molecular markers in juveniles of Nile tilapia exposed to chronic salinity stress. The tilapia were fed four experimental diets supplemented with 0, 1, 2, and 3% of L-arginine (T0, T1, T2, and T3). After an acclimatization period, the tilapias were exposed to a salinity level of 20‰ for 57 days in a recirculating aquaculture system. Our findings revealed that overall performance parameters were significantly influenced by L-arginine supplementation, except for the condition factor, viscerosomatic index, and hepatosomatic index. Additionally, intermediate levels of L-arginine supplementation positively influenced various blood parameters, including hematological profiles (hemoglobin and leukocytes), blood chemistry (total protein, albumin, globulin, and triglycerides), and the frequency of certain nuclear abnormalities. Furthermore, L-arginine supplementation appeared to regulate the expression of molecular markers related to stress and the immune system. In conclusion, this study indicates that L-arginine supplementation can help alleviate the chronic stress caused by salinity in juvenile Nile tilapia. Full article

Aim: Antibiotic de-escalation (ADE) is essential, but appears to be underperformed although being possible, which we refer to as a ‘missed opportunity’. We aimed to analyze the ADE missed opportunities in Gram-negative bloodstream infections (BSIs) in a setting with a high antimicrobial resistance profile. Methods: A retrospective, two-centered cohort study was performed from 1 January 2018 to 30 June 2019, including adults with mono- or polymicrobial Gram-negative BSIs. All ADE episodes and 30-day mortality were noted. Results/Discussion: Out of 273 BSIs (43 ADE vs. 230 no-ADE episodes), 101 were considered a ‘missed’ opportunity of ADE (36.9%, 101/273). In multivariate analysis, ADE opportunities were missed 4.4 times more (OR = 4.4; 95% CI 1.24–15.9) in the presence of hematological malignancy and 6.2 times more (OR = 6.2; 95% CI 1.76–22.2) in ESBL. Contrary to this, ADE opportunities were missed 0.24 times less (OR = 0.24; 95% CI 0.09–0.61) among patients with E. coli BSIs, and 0.17 less (OR = 0.17; 95% CI 0.05–0.67) if ertapenem was used as an empirical agent. The ADE missed opportunity group had a higher mortality rate, which is statistically significant in univariate analysis, but not in multivariate analysis. Conclusion: The presence of ESBL and hematological malignancy were the significant barriers to appropriate ADE practice in our study. A good stewardship program must address physician hesitation in ADE practice. Full article

Clozapine, a second-generation antipsychotic known for its effectiveness in treating resistant schizophrenia, is often linked with serious hematological side effects, particularly neutropenia and agranulocytosis. This review investigates the underlying pathophysiological mechanisms of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA), outlines associated risk factors, and evaluates current clinical management strategies. Clozapine’s pharmacological profile, marked by its antagonism of dopamine D4 and serotonin receptors, contributes to both its therapeutic advantages and hematological toxicity. Epidemiological data show a prevalence of CIN and CIA at approximately 3.8% and 0.9%, respectively, with onset typically occurring within the first six months of treatment. Key risk factors include older age, Asian and African American ethnicity, female sex, and certain genetic predispositions. The development of CIN and CIA may involve bone marrow suppression and autoimmune mechanisms, although the exact processes remain partially understood. Clinical presentation often includes nonspecific symptoms such as fever and signs of infection, necessitating regular hematological monitoring in accordance with established guidelines. Management strategies include dosage adjustments, cessation of clozapine, and the administration of granulocyte colony-stimulating factors (G-CSF). Advances in pharmacogenomics show promise for predicting susceptibility to CIN and CIA, potentially improving patient safety. This review emphasizes the importance of vigilant monitoring and personalized treatment approaches to reduce the risks associated with clozapine therapy. Full article

Background and Objectives: Thrombocytopenia and hemolytic anemia are common but non-criteria manifestations of antiphospholipid syndrome (APS). However, their relationship with specific immunological profiles remains poorly characterized. This study aimed to evaluate these hematologic manifestations and identify their serological associations in patients with APS. Materials and Methods: We retrospectively reviewed 346 patients diagnosed with APS. Demographic, clinical, and laboratory characteristics were analyzed. Logistic regression was used to identify risk factors associated with hemolytic anemia. Results: The mean age was 47.1 ± 13.1 years, and 71.7% were female. Thrombocytopenia was present in 34.5%, and hemolytic anemia in 16.5% of patients. Lupus anticoagulant (LAC) was the most common antibody (66.8%). In univariate analysis, hemolytic anemia was significantly associated with LAC positivity (OR 4.216, 95% CI: 2.326–7.640, p < 0.001), anticardiolipin IgG (OR 7.170, p = 0.007), triple positivity (OR 3.638, p = 0.002), and diabetes mellitus (OR 2.084, p = 0.007). DIAPS showed a protective trend (OR 0.547, p = 0.002). In multivariate analysis, only LAC remained an independent risk factor for hemolytic anemia (adjusted OR 3.557, 95% CI: 1.355–9.335, p = 0.003). Conclusions: LAC positivity is an independent predictor of hemolytic anemia in APS. These findings suggest a distinct immunologic profile among patients with hematologic involvement and highlight the need for further investigation into non-criteria manifestations. Full article

Background: Pulsed field ablation (PFA) is a novel non-thermal modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF), offering myocardial selectivity through irreversible electroporation while sparing surrounding structures. However, concerns have emerged regarding potential subclinical hemolysis, reflected by alterations in biochemical markers such as lactate dehydrogenase (LDH). Methods: We conducted a retrospective, single-center study involving 249 patients undergoing PVI: 121 treated with PFA (PulseSelect or FARAPULSE) and 128 with radiofrequency (RF) ablation (PVAC catheter). Laboratory parameters were assessed at baseline, post-procedure, and at discharge, including hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, creatinine, and LDH. The primary endpoint was the variation in blood cell indices; the secondary endpoint was the evaluation of LDH and hematocrit changes. Statistical analysis included t-tests and chi-square tests. Results: Baseline characteristics and pre-procedural labs did not differ significantly between groups. No significant changes in hemoglobin, hematocrit, RBC count, platelet count, or creatinine were observed post-ablation or at discharge. However, LDH levels significantly increased in the PFA group both post-procedurally and at discharge (p < 0.001), without concurrent changes in other blood cell parameters. Conclusions: PFA and RF ablation yield comparable hematological profiles after PVI, with no significant impact on key blood cell parameters. Nonetheless, the consistent rise in LDH levels in the PFA group suggests mild, subclinical hemolysis or tissue injury due to more extensive lesions. While supporting the hematologic safety of PFA, these findings underscore the need for further studies to assess the clinical significance of these biochemical alterations, particularly in high-risk patients or extensive ablation settings. Full article